ABSTRACT This K01 proposal will provide Dr. Young-Wolff with the protected time and training she needs to transition to an independently funded researcher in the field of prenatal substance use (SU). Dr. Young-Wolff is a clinical psychologist and Research Scientist at the Kaiser Permanente Northern California (KPNC) Division of Research (DOR). The proposal builds on her background in preventing and treating SU in vulnerable populations and leverages the rich training environment afforded by DOR and the University of California, San Francisco to improve our understanding and treatment of prenatal SU. Prenatal SU has reached epidemic proportions. Up to half of women report illicit drug use, alcohol use, or cigarette smoking at some point during pregnancy. This is troubling as prenatal SU has significant and devastating consequences to both mother and infant. Existing research on prenatal SU, however, is often limited to older, self-reported data with women selected for SU screening based on clinician judgement, leaving the true scope of the problem unclear. Using KPNC?s rich electronic health record, the proposed study addresses these limitations using gold-standard (self-report and urine toxicology) data from universal prenatal SU screening with >376,000 pregnant women. Specifically, this study will: 1) establish trends in prenatal substance and polysubstance use from 2009-2017, 2) develop predictive models using clinical and demographic characteristics to identify women at greatest risk for continued prenatal SU, and 3) conduct a qualitative study among women who quit vs. persisted in SU during pregnancy to identify barriers to and facilitators of quitting. With high potential to be scalable, findings will provide the foundation for two R01 studies. The first will examine specific perinatal and postnatal outcomes related to prenatal SU by trimester of exposure, accounting for polysubstance use and socioenvironmental risk factors, and the second will develop and test a SU intervention targeted to the needs of women at greatest risk for continuing SU during pregnancy. Dr. Young-Wolff?s career development goals outline parallel training that is critical to the success of her future research, including training in: 1) perinatal epidemiology and prenatal SU prevention, treatment and ethics, 2) predictive statistical modeling, 3) leveraging complex EHR-derived clinical data, and 4) qualitative methodologies. These goals will be accomplished through support from an outstanding team of mentors, formal didactics, seminars, meetings, and conferences. Importantly, the proposed work is realistic and feasible within the award period and will allow Dr. Young-Wolff to continue to build research skills, generate preliminary data, create additional collaborative relationships, and compete for R01 funding. In summary, this K01 award will support and accelerate the career development activities of Dr. Young-Wolff and allow her to successfully launch the next phase of her career as an independently funded investigator.